RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy and chemotherapy may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to study the effectiveness of radiation therapy and chemotherapy followed by surgery and combination chemotherapy in treating patients who have stage II or stage III rectal cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the rectum stage III rectal cancer stage II rectal cancer Quality of Life	Drug: fluorouracil  Drug: leucovorin calcium	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the local recurrence rate, disease-free survival, and overall survival of patients with stage II or III rectal cancer treated with neoadjuvant radiotherapy and fluorouracil followed by surgical resection and adjuvant fluorouracil and leucovorin calcium. II. Determine the toxicity rate in patients treated with this regimen. III. Correlate failure-free survival with ultrasound-determined preoperative staging in patients treated with this regimen. IV. Determine the quality of life of patients treated with this regimen. V. Determine if toxicity due to treatment, daily stool frequency, sexual dysfunction, and disease-free survival correlates with quality of life parameters in patients treated with this regimen. VI. Correlate clinical selection criteria with ability to perform sphincter-sparing surgery in patients treated with this regimen. VII. Determine post-chemoradiotherapy pathological response, margin status, and lymph node status and correlate these factors with initial clinico-pathologic findings in patients treated with this regimen.

PROTOCOL OUTLINE: Patients undergo pelvic radiotherapy once daily five days a week for 5 weeks followed by boost radiotherapy twice daily for 7 days. Patients also receive neoadjuvant fluorouracil IV continuously over days 1-4 and 36-40. Patients undergo surgical resection 4-6 weeks after completion of radiotherapy. At 4 weeks after surgery, patients receive adjuvant leucovorin calcium IV and fluorouracil IV once daily five days a week. Treatment continues every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the completion of pelvic and boost radiotherapy, at 4 weeks after completion of chemoradiotherapy (prior to surgery), and then at 3, 6, and 12 months after completion of study therapy. Patients are followed every 3 months for 2 years, every 4 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 23-41 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the rectum; Tumor extending through bowel wall (T3) OR Fixation to surrounding structures (T4) OR Nodal involvement by endorectal ultrasound (N1-2)
• Tumor extending through bowel wall but not fixed (T3) must be: At least 4 cm or at least 40% of bowel circumference OR Accompanied by nodal involvement
• Evidence of transmural penetration confirmed by 2 of the following: CT scan; Pelvic; MRI; Transrectal ultrasound; Physical exam
• Proximal extent of tumor must not extend higher than 12 cm above denate line and must be below pelvic peritoneal reflexion or sacral promontory
• Regional lymph node involvement allowed
• No distant metastases by CT scan of abdomen and pelvis or chest x-ray

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for rectal cancer
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy for rectal cancer
• Surgery: No prior surgery for rectal cancer except diagnostic biopsy

--Patient Characteristics--

• Age: Over 18
• Performance status: ECOG 0-1
• Life expectancy: At least 2 years
• Hematopoietic: Leukocyte count greater than 4,000/mm3; Platelet count at least 100,000/mm3; Hemoglobin greater than 10 g/dL
• Hepatic: SGOT and SGPT less than 1.5 times normal; Bilirubin less than 1.5 mg/dL
• Renal: Creatinine less than 1.8 mg/dL
• Other: Not pregnant or nursing; Negative pregnancy test; No other prior or concurrent malignancy within the past 5 years except inactive non-melanoma skin cancer or carcinoma in situ of the cervix; No psychiatric condition that would preclude informed consent; No other serious medical illness that would limit survival

New Jersey
      Community Medical Center, Toms River,  New Jersey,  08755,  United States
      Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County, Mount Holly,  New Jersey,  08060,  United States
      Hunterdon Regional Cancer Center, Flemington,  New Jersey,  08822,  United States
      Kimball Medical Center, Lakewood,  New Jersey,  08701,  United States
      Riverview Medical Center, Red Bank,  New Jersey,  07701,  United States
      St. Francis Medical Center, Trenton,  New Jersey,  08629,  United States
Pennsylvania
      Bon Secours-Holy Family Health System, Altoona,  Pennsylvania,  16602,  United States
      Conemaugh Memorial Hospital, Johnstown,  Pennsylvania,  15905,  United States
      Delaware County Memorial Hospital, Drexel Hill,  Pennsylvania,  19026,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      North Penn Hospital, Lansdale,  Pennsylvania,  19446,  United States
      Paoli Memorial Hospital, Paoli,  Pennsylvania,  19301-1792,  United States
      Pinnacle Health Hospitals, Harrisburg,  Pennsylvania,  17105-8700,  United States
      Pottstown Memorial Regional Cancer Center, Pottstown,  Pennsylvania,  19464,  United States
      Reading Hospital and Medical Center, Reading,  Pennsylvania,  19612-6052,  United States
      Saint Mary Regional Center, Langhorne,  Pennsylvania,  19047,  United States
      Southern Chester County Medical Center, West Grove,  Pennsylvania,  19390,  United States

Study chairs or principal investigators

Benjamin Movsas,  Study Chair,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000068776; FCCC-96071; NCI-G01-1988
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00021398
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08